[!INFO] Aspirin prophylaxis
"Women who are at high risk of developing pre-eclampsia should take aspirin 75mg od from 12 weeks until the birth of the baby." - NICE via Passmedicine
Current research demonstrates that improper trophoblast differentiation during endothelial invasion due to abnormal regulation and/or production of cytokines, adhesion molecules, major histocompatibility complex molecules, and metalloproteinases plays a key role in the development of a gestational hypertensive disease. Abnormal regulation and/or production of these molecules leads to abnormal development and remodeling of spiral arteries in the deep myometrial tissues. This leads to placental hypoperfusion and ischemia. More recent research shows role of antiangiogenic factors that are released by placental tissue cause SYSTEMIC ENDOTHELIAL DYSFUNCTION which can result in systemic hypertension. (in PIH, activity of angiogenic factors like VEGF and PlGF - placental growth factor - are reduced) Organ hypoperfusion from endothelial dysfunction is most commonly seen in the eyes, lungs, liver, kidneys and peripheral vasculature. Overall, most experts agree underlying reason is multifactorial
[!TIP] mnemonic: 'flozins' are SGLT-2 inhibitors
Glucose 'flowz in' the PCT
| Agent | Class | Mechanism | Side effects | Other stuff | Expected effect |
| ------------------------------------------------ | -------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Metformin | Biguanide | Insulin sensitiztion Reduce hepatic gluconeogenesis. | GI side effects Lactic acidosis (risk in renal/liver/heart failure – contrindications) No weight gain May reduce apetite, STOP when eGFR < 30 | Reduced GI B12 absorption The usual first line agent, can be combined with other | Lower FBS by about 50 mg/dL Lowers HbA1C by about 1% |
| Pioglitazone is the only one | Thiazolidinediones (glitazones) | Increases insulin sensitivity by binding nuclear receptors and altering gene expression may increase glucose consumption in muscle cells | no hypoglycaemia Commonly weight gain Fluid retention → precipitates Heart failure | May specifically benefit NAFLD | take up to 3 months to reach maximal effect. |
| Gliclazide Glimipiride Glibenclamide Tolbutamide | Sulphonylureas | Promotes depolarization of beta cell → stimulates insulin secretion (by binding ATP dependent k+ channel) | Weight gain! Hypoglycaemia | Effect will wear off with age as beta cell mass declines Risk of hypoglycaemia increases with age and intercurrent infection and duration of drug action Gliclazide / Glipizide / tolbutamide → Short acting Glimiperide → ? long acting but lower hypo risk Glyburide(= Glibenclamide) – long acting | Similar to metformin Weight gain of 1-4 Kg |
| Repaglinide | Meglitinides ("slp.ureas lite") | Post prandial insulin releasers (binds ATP dependent k+ channel like sulfonylureas) but act only for 3 hrs. So effective only in post prandial period when taken with meals | Hypoglycaemia Weight gain (but less than s.ureas) | Taken about 30 minutes before meals. | Less effective than other drugs. Role in DM Mx is not clear. Can be used with metformin is C/I or when patient only has post prandial hyperglycaemia |
| Sitagliptin Linigliptin | DPP-4 inhibitors (gliptins) | Inhibit GLP-1 breakdown (restore physiologic GLP levels) → promotion of insulin secretion GLP1 receptors are also found in the cardiovascular system | Good S/E profile. | Used as second line drug, in early DM when insulin secretion is still preserved. Combined with metformin / sulfonylurea | Modest effect but used because of low S/E profile. |
| Empagliflozin Dapagliflozin Canagliflozin | SGLT inhibitors | Inhibit the coupled reabsorption of sodium and glucose from the proximal tubules (+ other renal effects) | Dehydration Genital candidiasis (but not bacterial UTI),Can precipitate DKA (increase production of ketones) | Wonder drug! Decreases weight Improve renal dysfuntion – renoprotective Reduce atherosclerotic events! Reduce risk of heart failure | ?More potent glucose lowering than metformin(values given in K&C). Weight loss of 2-4 Kg over 1 year |
| GLP - Agonists - See Below | | | | | |
| | | | | | |
- *GI symptoms*
extrapulmonary manifestations:
Diagnosis: fastidious organism, use PCR
[!INFO] Ergot Vs. Non Ergot antiparkinson medications: Fibrosis Vs Non fibrotic
- Ergot derived antiparkinson medications: Pergolide, Lisuride, Bromocriptine and cabergoline
- Non ergot derived antiparkinson medication are the newer class: Ropinirole
- Others are pramipexole, ropinirole, rotigotine and apomorphine
- Ergot is a fungus which secretes psychoactive substances.
- Ergot derived antiparkinson mediations have increased risk of fibrotic reactions (pericardial, pleural, retroperitoneal) due to stimulation of serotonin receptors.
[!TIP] Mnemonic: Dopamine agonists
Ergot derived NON ergot Fungal PeLiCan B PramOnRottinRope Pergolide, Lisuride, Cabergoline, Bromocriptine pramipexole, ropinirole, rotigotine
- Common Side effect of levodopa and dopamine agonists. Can be due to *inadequate* DDC inhibitor. *Treat with domperidone* but *avoid metoclopramide* which *crosses the BBB*. Early side effect. Settles with time.
Apparently these tables were created by NICE. Found on Passmedicine.
| Effect | Levodopa |
Dopamine agonists |
MAO‑B inhibitors |
|---|---|---|---|
| Motor symptoms | More improvement in motor symptoms | Less improvement in motor symptoms | Less improvement in motor symptoms |
| Activities of daily living | More improvement in activities of daily living | Less improvement in activities of daily living | Less improvement in activities of daily living |
| Motor complications | More motor complications | Fewer motor complications | Fewer motor complications |
| Adverse events | Fewer specified adverse events* | More specified adverse events* | Fewer specified adverse events* |
| * side effects : excessive sleepiness, hallucinations and impulse control disorders |
"If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct. Again, NICE summarise the main points in terms of decision making:"
| Effect | Dopamine agonists | MAO‑B inhibitors | COMT inhibitors | Amantadine |
|---|---|---|---|---|
| Motor symptoms | Improvement in motor symptoms | Improvement in motor symptoms | Improvement in motor symptoms | No evidence of improvement in motor symptoms |
| Activities of daily living | Improvement in activities of daily living | Improvement in activities of daily living | Improvement in activities of daily living | No evidence of improvement in activities of daily living |
| Off time | More off‑time reduction | Off‑time reduction | Off‑time reduction | No studies reporting this outcome |
| Adverse events | Intermediate risk of adverse events | Fewer adverse events | More adverse events | No studies reporting this outcome |
| Hallucinations | More risk of hallucinations | Lower risk of hallucinations | Lower risk of hallucinations | No studies reporting this outcome |
And of course, my own table.
| Entacapone | Catachol-O-methyltransferase inhibitor (prevents peripheral degradation of levodopa) | Prolongs levodopa action - used to manage on/off phenomena + end of dose 'wearing off'; often combined with levodopa | Gastrointestinal and dyskinetic side effects |
[!INFO] See [[#Comparison of amoebiasis and giardiasis]] below
| Amoebiasis | Giardiasis | Cyclosporiasis |
|---|---|---|
| Protozoan | Protozoan | |
| Cyst is infective | Cyst is infective | |
| Cysts survive in environment | Cysts survive in environment | |
| faeco-oral transmission | Faeco-oral transmission | |
| Cysts resistant to gastric acid | Cyst resistant to chlorine | |
| Trophozoites cause disease | Same | |
| Invasive | Usually not invasive | Sporozoites invade small intestinal epithelial cells |
| Trophozoites localize in large intestine | Small intestine | Small intestine |
| Cyst ?immediately infective | Cyst immediately infective | Cyst must mature for days to weeks in environment -> human to human transmission unlikely. |
| Metronidazole / paromoycin | Tinidazole / metro | TMP + SMX |